Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
  • C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
• • C—CHEMISTRY; METALLURGY
  • C01—INORGANIC CHEMISTRY
  • C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
  • C01B33/00—Silicon; Compounds thereof
  • C01B33/20—Silicates
  • C01B33/26—Aluminium-containing silicates, i.e. silico-aluminates
  • C01B33/28—Base exchange silicates, e.g. zeolites
  • C01B33/2807—Zeolitic silicoaluminates with a tridimensional crystalline structure possessing molecular sieve properties; Isomorphous compounds wherein a part of the aluminium ore of the silicon present may be replaced by other elements such as gallium, germanium, phosphorus; Preparation of zeolitic molecular sieves from molecular sieves of another type or from preformed reacting mixtures
  • C01B33/2876—Zeolitic silicoaluminates with a tridimensional crystalline structure possessing molecular sieve properties; Isomorphous compounds wherein a part of the aluminium ore of the silicon present may be replaced by other elements such as gallium, germanium, phosphorus; Preparation of zeolitic molecular sieves from molecular sieves of another type or from preformed reacting mixtures from a reacting mixture containing an amine or an organic cation, e.g. a quaternary onium cation-ammonium, phosphonium, stibonium
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
  • C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
  • C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
  • C07D451/06—Oxygen atoms

Definitions

• This invention relates to tropane derivatives, their synthesis and their use.
• Tropane or 8-methyl-8-azabicyclo[3.2.1]octane, having the formula (I) wherein R' and R" are both hydrogen, is a known compound detailed in The Merck Index. 9th Ed., No. 9440. A number of substituted derivatives of tropane are also detailed in The Merck Index, 9th Ed., as follows:
• Tropentane No. 94 4 2 or 1-phenylcyclopentanecarbox- ylic acid 8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester, has the above formula wherein R' is hydrogen and R" is of the formula (II) and is prepared from tropine and 1-phenyl- cyclopentanecarboxyl chloride.
• Tropeine, No. 9441 is a name given esters of tropine in general, while tropine benzylate, No. 9447 or endo-alpha- hydroxy-alpha-phenylbenzeneacetic acid 8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester, has the above formula wherein R' is hydrogen and R" is of the formula (III).
• Tropacine No. 9 4 36 or endo-afpha-phenylben- zeneacetic acid 8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester, has the above formula wherein R' is hydrogen and R" is of the formula (IV) and is prepared from tropine. and diphenylacetyl chloride as described in Swiss Patent 202,181.
• Atropine, No. 892 or endo-( ⁇ )-alpha-(hydroxymethyl)-benzeneacetic acid 8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester has the above formula wherein R' is hydrogen and R" is of the formula (V).
• a quaternary ammonium tropane compound having the formula (VI) wherein R is alkyl of 1 to 10 carbon atoms, R' and R" are groups selected from formulae (I, II, III and IV above, hydrogen, hydroxide, alkyl of 1 to 10 carbon atoms alkenyl of 2 to 8 carbon atoms, ester (such as methyl acetate, ethyl acetate, n-propyl acetate, ethyl formate and ethyl propionate), ether (such as dimethyl ether and diethyl ether) and combinations thereof, and X is an anion selected from halide, (e.g. iodide, chloride or bromide), hydroxide, nitrate, perchlorate and bisulfate.
• R is alkyl of 1 to 10 carbon atoms
• R' and R" are groups selected from formulae (I, II, III and IV above, hydrogen, hydroxide, alkyl of 1 to
• the invention resides in a method for synthesizing a compound having the formula - (VI) wherein R is alkyl of 1 to 10 carbon atoms, R' and R" are radicals selected from those of formulae (II).
• X is an anion, which comprises forming a reaction mixture comprising from 5 to 20 weight percent tropane or a derivative thereof substituted at the 3 position by said radical(s), from 1 0 to 20 weight percent of an alkylating agent having 1 to 10 carbon atoms, and from 60 to 85 weight percent of a solvent and maintaining said mixture at reaction conditions of temperature and pressure sufficient to permit synthesis of said compound.
• the invention resides in a method of preparing a synthetic crystalline silicate material comprising a reaction mixture containing sources of an alkali metal or alkaline earth metal oxide, an oxide of silicon, an oxide of aluminum, water and a quaternary ammonium tropane compound or 3-substituted derivative thereof having the formula (VI) wherein R is alkyl of 1 to 10 carbon atoms, R' and R" are radicals selected from those of formulae (11), (III), (IV) and (V), hydrogen, hydroxyl, alkyl of 1 to 1 0 carbon atoms, alkenyl of 2 to 8 carbon atoms, ester, ether and combinations thereof and X is an anion, and maintaining said reaction mixture under sufficient crystallization conditions until crystals of said silicate material are formed.
• the present compounds are synthesized by alkylation selectively at the bridghead nitrogen of the starting material compound, examples of which are tropane, tropine, tropentane, tropine benzylate, tropacine and atropine.
• the R' and R" substituents may be the same of different, although preferably at least one of the substituents is hydrogen. Most preferably R' is hydrogen and R" is hydroxyl.
• Non-limiting examples of the compounds of this invention include compounds of methyltropinium, ethyltropinium, propyltropinium, butyltropinium, pentyltropinium, hexyl- tropinium, heptyitropinium, octyltropinium, nonyltropinium and decyttropinium.
• the alkyl substituent, R may be linear or branched, with linear preferred.
• the synthesis method utilized for preparation of the compounds of this invention involves contacting the appropriate starting material compound with an alkylating agent dissolved in a suitable solvent medium at reaction conditions including a temperature of from about ambient to reflux, and a pressure of from 100 to 3549 kPa - (atmospheric to 500 psig), preferably about 100 kPa - (atmospheric).
• reaction conditions including a temperature of from about ambient to reflux, and a pressure of from 100 to 3549 kPa - (atmospheric to 500 psig), preferably about 100 kPa - (atmospheric).
• the time required for the reaction will, of course, depend upon such factors as temperature and pressure, as well as relative concentrations of reactants and desired degree of reaction, but usually will be from 6 hours to 4 days.
• the reaction mixture will comprise from 5 to 20 weight percent tropane or 3-substituted derivative thereof, from 10 to 20 weight percent alkylating agent and from 60 to 85 weight percent solvent.
• the solvent is preferably polar and is suitably an alcohol of 1 to 8 carbon atoms, an ether of 2 to 10 carbon atoms, or a combination thereof, especially methanol, ethanol, acetone and/or diethyl ether.
• the tropane or 3- substituted derivative thereof shoufd be soluble in the solvent chosen to at least about 20 percent
• the preferred solvent will be essentially water-free, as will the reaction mixture in which the present compounds are produced.
• Choice of solvent will determine to a substantial degree the reflux temperature at which the reaction will proceed to produce the required quaternary ammonium tropane compound or 3-substituted derivative thereof. For example, for an ethanol solvent, the reflux temperature will be about 70°C, whereas for a methanol solvent the reflux temperature will be about 65°C.
• the alkylating agent may be an olefin such as, for example, ethylene, propylene, butene, decene, formaldehyde, an alkyl halide or an alcohol, provided the alkyl portion thereof has from 1 to 10 carbon atoms Numerous other acyclic compounds able to provide at least one reactive C, to C 10 alkyl radical may be utilized as alkylating agents.
• the preferred alkylating agent is alkyl halide of from 1 to 10 carbon atoms, especially the chloride, bromide or iodide, with iodide preferred. When an alkyl halide is used, the halide moiety wilt of course be the anion of the compound of the invention.
• silicates are useful as catalyst components, sorbents and/or ion exchangers.
• Such silicates are prepared from a reaction mixture containing sources of an alkali or alkaline earth metal oxide, an oxide of aluminum, an oxide of silicon, water and the directing agent compound, as is exemplified hereinafter.
• Such reaction mixture will have a composition, in terms of mole ratios of oxides, within the following ranges: wherein R"' is the cation of the directing agent compound - (VI) and M is the alkali or alkaline earth metal cation.
• Crystallization of the silicate can be carried out under either static or stirred condition in a suitable reactor vessel, such as for example, polypropylene jars or teflon lined or stainless steel autoclaves.
• the temperature range for the silicate crystallization is generally from 100°C to 200°C for a time sufficient for crystallization to occur at the temperature used, e.g. from 48 hours to 15 days. Thereafter, the crystals are separated from the liquid and recovered.
• the reaction mixture can be prepared utilizing materials which supply the appropriate oxides. Such materials may include sodium silicate, silica hydrosol, silica gel, silicic acid, sodium hydroxide, a source of aluminum, and the directing agent compound.
• reaction mixture oxides can be supplied by more than one source.
• the reaction mixture can be prepared either batchwise or continuously. Crystal size and crystallization time of the crystalline silicate material will vary with the nature of the reaction mixture employed and the crystallization conditions.
• Alkyltropinium halides i.e., iodides
• VI reaction
• R was individually methyl, ethyl, propyl, butyl and pentyl.
• the reaction mixture was generally refluxed for 1-3 days before quenching the reaction vessel in a dry ice- acetone bath to -20°C.
• the crystalline product was separated from the solvent and filtered on a Buchner funnel. The crystals were dried in an air stream, then chemically analyzed.
• Table 1 records the analytical results for the series of alkyltropinium iodides synthesized in these examples.
• Example 6 The product of Example 6 was found to be a crystalline silicate having a particular X-ray diffraction pattern with a trace of unidentified second component impurity.
• the products from Examples 7-11 proved to be 100 percent crystalline silicate having the same X-ray diffraction pattern as that of Example 6.
• the crystalline silicate of Examples 6-11, designated ZSM-58, is described in more detail in our copending Application No._(corresponding to U.S. Patent Application No. 705821, Mobil Docket F-3364).
• Example 9 The X-ray diffraction pattern of the Example 9 crystals, after calcination at 538°C for 17 hours in air, is set forth as illustration in Table 3. Other properties of each crystalline product are presented in Table 4. In the latter table, compositions are calculated on the basis of 100 (SiO 2 + AlO 2 - ) tetrahedra. The as-synthesized crystalline materials contained from 3.8 to 5.0 methyttropinium cations per 1 00 tetrahedra.
• Example 9 product crystals having been calcined in nitrogen for 4 hours at 500°C, ammonium exchanged and converted to the hydrogen form, was subjected to the sorption test. Significant n-hexane, i.e. 8 weight percent at 90°C, was sorbed while only minimal cyclohexane (about 1 weight percent at 90°C) sorbed at 80 torr hexane partial pressure. This indicates molecular shape selectivity, a very valuable propertyfor the crystalline silicate directed by the methyltropinium iodide of Example 1.
• Example 9 product used for sorption evaluation was evaluated in the Alpha Test. Its Alpha Value proved to be 13 at 538°C.
• the solid products were analyzed by x-ray diffraction and chemical analysis.
• the solid crystalline silicate products of Examples 14-21 were of zeolite ZSM-5 structure see (U.S. Patent 3,702,886 of varying crystallinity, as recorded in Table 5.
• the product of Example 17 also contained alpha-quartz.

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• Chemical & Material Sciences (AREA)
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• Inorganic Chemistry (AREA)
• Silicates, Zeolites, And Molecular Sieves (AREA)
• Nitrogen Condensed Heterocyclic Rings (AREA)
• Solid-Sorbent Or Filter-Aiding Compositions (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

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Citations (13)

• 1986
  • 1986-01-29 EP EP86300582A patent/EP0195498A3/fr not_active Withdrawn
  • 1986-02-25 JP JP3842486A patent/JPS61200986A/ja active Pending

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